Antiphospholipid syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Antiphospholipid syndrome is a disorder characterized by an increased tendency to form abnormal blood clots (thromboses) that can block blood vessels. This clotting tendency is known as thrombophilia. In antiphospholipid syndrome, the thromboses can develop in nearly any blood vessel in the body. If a blood clot forms in the vessels in the brain, blood flow is impaired and can lead to stroke. Antiphospholipid syndrome is an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs.

Women with antiphospholipid syndrome are at increased risk of complications during pregnancy. These complications include pregnancy-induced high blood pressure (preeclampsia), an underdeveloped placenta (placental insufficiency), early delivery, or pregnancy loss (miscarriage). In addition, women with antiphospholipid syndrome are at greater risk of having a thrombosis during pregnancy than at other times during their lives. At birth, infants of mothers with antiphospholipid syndrome may be small and underweight.

A thrombosis or pregnancy complication is typically the first sign of antiphospholipid syndrome. This condition usually appears in early to mid-adulthood but can begin at any age.

Other signs and symptoms of antiphospholipid syndrome that affect blood cells and vessels include a reduced amount of cells involved in blood clotting called platelets (thrombocytopenia), a shortage of red blood cells (anemia) due to their premature breakdown (hemolysis), and a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. In addition, affected individuals may have open sores (ulcers) on the skin, migraine headaches, or heart disease. Many people with antiphospholipid syndrome also have other autoimmune disorders such as systemic lupus erythematosus.

Rarely, people with antiphospholipid syndrome develop thromboses in multiple blood vessels throughout their body. These thromboses block blood flow in affected organs, which impairs their function and ultimately causes organ failure. These individuals are said to have catastrophic antiphospholipid syndrome (CAPS). CAPS typically affects the kidneys, lungs, brain, heart, and liver, and is fatal in over half of affected individuals. Less than 1 percent of individuals with antiphospholipid syndrome develop CAPS.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

The genetic cause of antiphospholipid syndrome is unknown. This condition results from the presence of three abnormal immune proteins (antibodies) in the blood. The antibodies that cause antiphospholipid syndrome are called lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I. These antibodies are referred to as antiphospholipid antibodies. People with this condition can test positive for one, two, or all three antiphospholipid antibodies in their blood. Antibodies normally attach (bind) to specific foreign particles and germs, marking them for destruction, but the antibodies in antiphospholipid syndrome attack normal human proteins. When these antibodies attach to proteins, the proteins change shape and attach to other molecules and receptors on the surface of cells. Attaching to cells, particularly immune cells, turns on (activates) the blood clotting pathway and other immune responses.

The production of the antiphospholipid antibodies may coincide with exposure to foreign invaders, such as viruses and bacteria, that are similar to normal human proteins. Exposure to these foreign invaders may cause the body to produce antibodies to fight the infection, but because the invaders are so similar to the body's own proteins, the antibodies also attack the human proteins. Similar triggers may occur during pregnancy when a woman's physiology, particularly her immune system, adapts to accommodate the developing fetus. These changes during pregnancy may explain the high rate of affected females.

Certain genetic variations (polymorphisms) in a few genes have been found in people with antiphospholipid syndrome and may predispose individuals to produce the specific antibodies known to contribute to the formation of thromboses. However, the contribution of these genetic changes to the development of the condition is unclear.

People who repeatedly test positive for any of the antiphospholipid antibodies but have not had a thrombosis or recurrent miscarriages are said to be antiphospholipid carriers. These individuals are at greater risk of developing a thrombosis than is the general population. The risk is especially high in people who test positive for all three antiphospholipid antibodies (triple-positive).

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of antiphospholipid syndrome are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing antiphospholipid syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Antiphospholipid syndrome is estimated to affect 1 in 2,000 people. This condition may be responsible for up to one percent of all thromboses. It is estimated that 20 percent of individuals younger than age 50 who have a stroke have antiphospholipid syndrome. Ten to 15 percent of people with systemic lupus erythematosus have antiphospholipid syndrome. Similarly, 10 to 15 percent of women with recurrent miscarriages likely have this condition. Approximately 70 percent of individuals diagnosed with antiphospholipid syndrome are female.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Intrauterine growth retardation · Very frequent (99-80%)

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Anti-beta 2 glycoprotein I antibody positivity · Frequent (79-30%)

Presence of antibodies against beta 2 glycoprotein I in the circulation. Beta-2 glycoprotein I (beta2GPI) is the principal target of autoantibodies in the antiphospholipid syndrome (APS).

Anti-beta-2-Glycoprotein I IgG antibody positivity · Frequent (79-30%)

Presence of IgG antibodies against beta 2 glycoprotein I in the circulation. Beta-2 glycoprotein I (beta2GPI) is the principal target of autoantibodies in the antiphospholipid syndrome.

Anti-beta-2-Glycoprotein I IgM antibody positivity · Frequent (79-30%)

Presence of IgM antibodies against beta 2 glycoprotein I in the circulation. Beta-2 glycoprotein I (beta2GPI) is the principal target of autoantibodies in the antiphospholipid syndrome.

Anticardiolipin IgG antibody positivity · Frequent (79-30%)

The presence of circulating IgG autoantibodies to cardiolipin.

Anticardiolipin IgM antibody positivity · Frequent (79-30%)

The presence of circulating IgM autoantibodies to cardiolipin.

Antiphospholipid antibody positivity · Frequent (79-30%)

The presence of circulating autoantibodies to phospholipids.

Arterial thrombosis · Frequent (79-30%)

The formation of a blood clot inside an artery.

Other findings in the same source

From: Orphanet

Additional reported features include Fatigue (Frequent (79-30%)); Hypercoagulability (Frequent (79-30%)); Hypertension (Frequent (79-30%)); Ischemic stroke (Frequent (79-30%)); Livedo racemosa (Frequent (79-30%)); Livedo reticularis (Frequent (79-30%)); Lupus anticoagulant (Frequent (79-30%)); Pain (Frequent (79-30%)); Preeclampsia (Frequent (79-30%)); Premature birth (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Antiphospholipid syndrome is Rheumatology, with a rheumatologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Antiphospholipid syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.